Fig. 2

Index case CDKN2A: Established cell line array comparative genomic hybridization and formalin-fixed paraffin-embedded tumor FISH. a Established cell line detailed array comparative genomic hybridization profile for 9p21.3 locus showing the 143 kb homozygous deletion (log2 ratio 2 = − 4) involving CDKN2A gene. Notice the two break points ‘sharp’ profile of the homozygous deletion characterized by sudden shift from a normal copy number status to a homozygous deletion (see text). The vertical red line on the right indicates the position of the 222 kb Vysis locus specific CDKN2A FISH probe employed. Notice that MTAP gene in not included in the region of homozygous deletion. b Tumor tissue section from the index case hybridized with the Vysis CDKN2A Spectrum Orange/CEP9 Spectrum Green probe (counterstained with DAPI). Tumor cells display two signals of both CDKN2A and CEP9. A nontumor cell and a tumor cell are highlighted in white and yellow boxes, respectively, and shown at higher magnification. CDKN2A FISH signals are diminished in the tumor cells compared with nontumor cells. Figure 1B inset: Box plot representing the distribution of FISH signal size in nontumor(WT) and tumor(dim) cells (p = 0.000126). c Tumor tissue section from the index case. Immunohistochemistry indicating P16 complete loss of expression (upper panel) and preservation of MTAP expression (lower panel)